The ability of polarized epithelia to alter their cellular organization to accommodate the formation of complex structures is essential for the proper formation of almost all tissues and organs in the vertebrate embryo. The research put worth in this proposal will investigate the mechanistic basis for how cells control morphology and architecture during development, by elucidating the genetic, cell biological, and biochemical properties of Shroom family proteins during embryogenesis and adult life. The Shroom family of cytoskeletal-associated proteins has been linked to controlling cellular morphogenesis during vertebrate embryogenesis in humans, mice, and frogs, as defects in these genes cause neural tube defects and X-linked mental retardation. The specific aims of this proposal are as follows: Aim I: Utilize genetic approaches in mice to define the in vivo functions of Shroom2 and Shroom3. Aim II: Define the mechanism by which each of the Shroom family proteins are regulated. Aim III: identify the cellular factors that link Shroom3 to myosin-dependent changes in cell shape and architecture. Aim IV: Determine the cellular basis for the genetic interactions between Shroom3 and the PCP pathway in neural morphogenesis. These aims address the hypothesis that Shroom family proteins function through a defined set of proteinacious networks and pathways to specify epithelial behaviors and characteristics, such as cell morphology and organization, that culminate in establishment of the correct vertebrate body plan and tissue architecture.The research in my lab utilizes a combination of approaches to understand the relationship between specific cellular behaviors and proper embryonic development and how errors in these processes can result in birth defects or embryonic lethality. We will continue to use in vivo studies in mice and in vitro studies in cell culture to understand the molecular mechanisms underlying human birth defects.